Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland.
School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland.
Histopathology. 2024 Aug;85(2):224-243. doi: 10.1111/his.15192. Epub 2024 Apr 17.
Tumour budding (TB) is a marker of tumour aggressiveness which, when measured in rectal cancer resection specimens, predicts worse outcomes and response to neoadjuvant therapy. We investigated the utility of TB assessment in the setting of neoadjuvant treatment.
A single-centre, retrospective cohort study was conducted. TB was assessed using the hot-spot International Tumour Budding Consortium (ITBCC) method and classified by the revised ITBCC criteria. Haematoxylin and eosin (H&E) and AE1/AE3 cytokeratin (CK) stains for ITB (intratumoural budding) in biopsies with PTB (peritumoural budding) and ITB (intratumoural budding) in resection specimens were compared. Logistic regression assessed budding as predictors of lymph node metastasis (LNM). Cox regression and Kaplan-Meier analyses investigated their utility as a predictor of disease-free (DFS) and overall (OS) survival. A total of 146 patients were included; 91 were male (62.3%). Thirty-seven cases (25.3%) had ITB on H&E and 79 (54.1%) had ITB on CK assessment of biopsy tissue. In univariable analysis, H&E ITB [odds (OR) = 2.709, 95% confidence interval (CI) = 1.261-5.822, P = 0.011] and CK ITB (OR = 2.165, 95% CI = 1.076-4.357, P = 0.030) predicted LNM. Biopsy-assessed H&E ITB (OR = 2.749, 95% CI = 1.258-6.528, P = 0.022) was an independent predictor of LNM. In Kaplan-Meier analysis, ITB identified on biopsy was associated with worse OS (H&E, P = 0.003, CK: P = 0.009) and DFS (H&E, P = 0.012; CK, P = 0.045). In resection specimens, CK PTB was associated with worse OS (P = 0.047), and both CK PTB and ITB with worse DFS (PTB, P = 0.014; ITB: P = 0.019). In multivariable analysis H&E ITB predicted OS (HR = 2.930, 95% CI = 1.261-6.809) and DFS (HR = 2.072, 95% CI = 1.031-4.164). CK PTB grading on resection also independently predicted OS (HR = 3.417, 95% CI = 1.45-8.053, P = 0.005).
Assessment of TB using H&E and CK may be feasible in rectal cancer biopsy and post-neoadjuvant therapy-treated resection specimens and is associated with LNM and worse survival outcomes. Future management strategies for rectal cancer might be tailored to incorporate these findings.
肿瘤芽（TB）是肿瘤侵袭性的标志物，当在直肠肿瘤切除标本中测量时，可预测更差的结果和对新辅助治疗的反应。我们研究了在新辅助治疗环境中评估 TB 的效用。
进行了一项单中心、回顾性队列研究。使用热点国际肿瘤芽协作组（ITBCC）方法评估 TB，并根据修订的 ITBCC 标准进行分类。比较活检中 TB（肿瘤内芽）的苏木精和伊红（H&E）和 AE1/AE3 细胞角蛋白（CK）染色与切除标本中 PTB（肿瘤周围芽）和 ITB（肿瘤内芽）的 ITB（肿瘤内芽）。逻辑回归评估芽作为淋巴结转移（LNM）的预测因子。Cox 回归和 Kaplan-Meier 分析探讨了它们作为无病（DFS）和总（OS）生存预测因子的效用。共纳入 146 例患者；91 例为男性（62.3%）。37 例（25.3%）在 H&E 上有 ITB，79 例（54.1%）在 CK 评估活检组织时有 ITB。在单变量分析中，H&E ITB[比值比（OR）=2.709，95%置信区间（CI）=1.261-5.822，P=0.011]和 CK ITB（OR=2.165，95%CI=1.076-4.357，P=0.030）预测 LNM。活检评估的 H&E ITB（OR=2.749，95%CI=1.258-6.528，P=0.022）是 LNM 的独立预测因子。在 Kaplan-Meier 分析中，活检中发现的 ITB 与较差的 OS（H&E，P=0.003，CK：P=0.009）和 DFS（H&E，P=0.012；CK，P=0.045）相关。在切除标本中，CK PTB 与较差的 OS 相关（P=0.047），CK PTB 和 ITB 与较差的 DFS 相关（PTB，P=0.014；ITB：P=0.019）。在多变量分析中，H&E ITB 预测 OS（HR=2.930，95%CI=1.261-6.809）和 DFS（HR=2.072，95%CI=1.031-4.164）。切除标本中 CK PTB 分级也独立预测 OS（HR=3.417，95%CI=1.45-8.053，P=0.005）。
使用 H&E 和 CK 评估 TB 在直肠肿瘤活检和新辅助治疗后处理的切除标本中可能是可行的，与 LNM 和较差的生存结果相关。未来直肠肿瘤的治疗策略可能需要根据这些发现进行调整。
